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Spinal microglia and neuropathic pain

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While spinal microglia do not interfere with the nociceptive response in normal conditions, they are actively involved in the development and maintenance of chronic pain following nerve injury in male, but not female animals.

Microglia are a type of glial cells located throughout the brain and spinal cord. They do not directly transmit neuronal signals, but they actively talk with surrounding neurons to modulate their activities. We have observed previously that shortly after an injury to peripheral nerve, spinal microglia become activated, and this activation is long-lasting for at least several months in rodents. Activated microglia are more prominent in releasing inflammatory mediators. To determine the crucial role of microglia in nerve injury-triggered neuropathic pain, we selectively depleted spinal microglia in normal animals and in animals having nerve injury, at acute and chronic phases.

Activated spinal microglia in a mouse with nerve injury

Our results first revealed that depleting spinal microglia does not directly affect neuronal activity nor their nociceptive response in normal conditions. However, microglia depletion at 2 weeks post-injury completely reverses injury-associated mechanical and cold hypersensitivity. Furthermore, neuropathic pain behavior is also significantly improved in nerve injured animals when their microglia are depleted 3 months after the insult. Thus, microglia are not only required for the development of neuropathic pain, but also needed for the maintenance. Yet, microglia could use different signaling molecules in the development and maintenance of neuropathic pain, since blocking microglia derived-inflammatory mediators, e.g., cytokines, is only effective in alleviating abnormal pain behavior at acute phase, but not at chronic phase. By using different pharmacological and genetic strategies, we also demonstrated that strikingly, the involvement of spinal microglia in neuropathic pain is only valid in males, but not in females.

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